Publication — IRIC

Starvation-induced proteasome assemblies in the nucleus link amino acid supply to apoptosis.

Eukaryotic cells have evolved highly orchestrated protein catabolic machineries responsible for the timely and selective disposal of proteins and organelles, thereby ensuring amino acid recycling. However, how protein degradation is coordinated with amino acid supply and protein synthesis has remained largely elusive. Here we show that the mammalian proteasome undergoes liquid-liquid phase separation in the nucleus upon amino acid deprivation. We termed these proteasome condensates SIPAN (Starvation-Induced Proteasome Assemblies in the Nucleus) and show that these are a common response of mammalian cells to amino acid deprivation. SIPAN undergo fusion events, rapidly exchange proteasome particles with the surrounding milieu and quickly dissolve following amino acid replenishment. We further show that: (i) SIPAN contain K48-conjugated ubiquitin, (ii) proteasome inhibition accelerates SIPAN formation, (iii) deubiquitinase inhibition prevents SIPAN resolution and (iv) RAD23B proteasome shuttling factor is required for SIPAN formation. Finally, SIPAN formation is associated with decreased cell survival and p53-mediated apoptosis, which might contribute to tissue fitness in diverse pathophysiological conditions.

Publication date
November 30, 2021
Principal Investigators
Uriarte M, Sen Nkwe N, Tremblay R, Ahmed O, Messmer C, Mashtalir N, Barbour H, Masclef L, Voide M, Viallard C, Daou S, Abdelhadi D, Ronato D, Paydar M, Darracq A, Boulay K, Desjardins-Lecavalier N, Sapieha P, Masson JY, Sergeev M, Kwok B, Hulea L, Mallette FA, Milot E, Larrivée B, Wurtele H, Affar EB
PubMed reference
Nat Commun 2021;12(1):6984
PubMed ID
34848715
Affiliation
Department of Biochemistry and Molecular Medicine, University of Montréal, H3C 3J7, Montreal, QC, Canada.